Treatment-resistant depression: Neurobiological correlates and the effect of sleep deprivation with sleep phase advance for the augmentation of pharmacotherapy

Objectives: To assess the neurobiology of treatment-resistant depression (TRD), and factors connected with improvement after total sleep deprivation (TSD) with sleep phase advance (SPA), for the augmentation of pharmacotherapy. Methods: The study comprised 43 patients with TRD, (15 male, 28 female), aged 48 +/- 13 years, with the illness duration 12 +/- 9 years, and the depressive episode 8 +/- 7 months. TRD was defined as a lack of significant improvement despite at least two antidepressant treatments and the augmentation with mood-stabilisers. Clinical improvement (response) was a reduction of >= 50% of points in the Hamilton Depression Rating Scale (HDRS), and the remission criterion was <= 7 points in HDRS, lasting until the 14th day after TSD + SPA. Results: TRD severity was associated with greater activity of the hypothalamic-pituitary-adrenal axis, the pro-inflammatory status of the immune system and lower reactivity of the hypothalamic-pituitary-thyroid axis. The response was achieved by 18 of 42 subjects, and connected with the later onset and shorter duration of the disease. In responders, there was a decrease in cortisol and interferon-gamma. In all subjects, a decrease in thyroid hormones was observed. Conclusions: TRD can improve after augmentation of pharmacotherapy by TSD + SPA and some biological changes may be compatible with a decrease in allostatic load.